Socioeconomic Deprivation, Genetics and Risk of Dementia

Abstract

AbstractBackgroundThe risk of Alzheimer’s disease and other subtypes of dementia is determined by multiple pathways including genetic, environmental and lifestyle factors. With higher risk in socioeconomically deprived individuals, it remains unclear whether associations of genetic risk with dementia incidence may be modified by individual‐ or area‐level socioeconomic deprivation.MethodParticipants of the UK Biobank study attended baseline assessments at 22 assessment centers between 2006 and 2010 and were followed‐up until 2016 or 2017. Cox proportional‐hazards regressions with area‐level socioeconomic deprivation based on the Townsend Deprivation Index and individual‐level socioeconomic deprivation based on car and home ownership, housing type, and income were run. A comprehensive polygenic risk score was employed and potential mediation through lifestyle and depressive symptoms was assessed. In an imaging substudy, associations of socioeconomic deprivation with six imaging‐derived phenotypes including white matter hyperintensities were examined.Result196,368 participants (mean [standard deviation] age, 64.1 [2.9] years, 52.7% female) aged 60 years and older, of European ancestry, without dementia diagnosis or cognitive impairment at baseline were followed‐up for 1,545,316 person‐years (median [interquartile range] follow‐up, 8.0 [7.4‐8.6] years). In high genetic risk and high area‐level deprivation 1.71% (95% confidence interval, 1.44% to 2.01%) developed dementia compared to 0.56% (95% confidence interval, 0.48% to 0.65%) in low genetic risk and low‐to‐moderate area‐level deprivation (hazard ratio, 2.31; 95% confidence interval, 1.84 to 2.91). In high genetic risk and high individual‐level deprivation 1.78% (95% confidence interval, 1.50% to 2.09%) developed dementia compared to 0.31% (95% confidence interval, 0.20% to 0.45%) in low genetic risk and low individual‐level deprivation (hazard ratio, 4.06; 95% confidence interval, 2.63 to 6.26). There was no significant interaction between genetic risk and area‐level (P =.77) or individual‐level (P =.07) deprivation. An imaging substudy including 11,083 participants found greater burden of white matter hyperintensities associated with higher socioeconomic deprivation.ConclusionIn older adults without dementia area‐level and individual‐level socioeconomic deprivation and genetic risk were significantly and independently associated with a higher risk of dementia. Dementia prevention interventions may be particularly effective if targeted to people living in deprived households and areas, regardless of genetic vulnerability.